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Cellular Rejuvenation Successfully Reverses Aging in Mice

March 3, 2022

Cellular rejuvenation could be the key to reversing aging after successful trials on mice.
By introducing reprogramming molecules known as Yamanaka factors, scientists were able to reverse aging in mice cells.
The study could have immense applications in tackling the aging process in human beings, as well as age-related diseases.

Can we reverse the aging process by simply rebooting our cells to more youthful states? That’s the question that scientists set out to answer through a joint research study between the Salk Institute and Genentech—a member of the Roche Group. Using cells from middle-aged and elderly mice, the scientists successfully reversed the aging process by partially resetting the cells through cellular rejuvenation. They added a mixture of four reprogramming molecules known as Yamanaka factors to the cells. These reprogramming molecules – Oct4, Sox2, Klf4, and cMyc – were observed to reset epigenetic marks in cells to their original patterns. Scientists were able to wind back the clock in adult cells into stem cells, and reprogram them back to their youthful states. But this is not the first time that Izpisua Belmonte, the lead professor in Salk’s Gene Expression Laboratory and holder of the Roger Guillemin Chair, has observed the effects of Yamanaka factors on cellular rejuvenation. In 2016, his lab reported that Yamanaka factors could be used to increase the lifespan of mice with a premature aging disease by countering the signs of aging. Recently, the team even discovered that Yamanaka factors in young mice can accelerate muscle regeneration. His research has also enabled other researchers to use a similar approach in improving the function of other tissues such as the optic nerve, brain, and heart. In the new study, Belmonte and his team analyzed the effects of different variations of Yamanaka factors on healthy animals as they aged. In one group of mice, Yamanaka factors were given in regular doses between the age of 15 months to 22 months; roughly the same age as humans between 50 to 70 years. Another group received regular doses between 12 to 22 months, about 35 to 70 human years. And the final group was treated for just a month after 25 months, about the same age as an 80-year-old person. When compared to the control mice, none of the mice receiving doses exhibited any neurological changes, blood altercations, or cancers. “What we really wanted to establish was that using this approach for a longer time span is safe. Indeed, we did not see any negative effects on the health, behavior, or body weight of these animals,” noted Pradeep Reddy, co-first author of the new study. When the researchers observed the regular indicators of aging in the mice that had received doses, they found the mice somewhat resembled younger animals. For example, the epigenetic profile of the skin and kidneys of the treated animals resemble the epigenetic patterns of younger mice. Skin cells of the treated animals also showed a greater ability to proliferate and avoid permanent scarring when injured. And lastly, the metabolic molecules of the treated animals did not show any of the normal age-related changes. However, this youthfulness was only documented in animals that received regular doses for seven to 10 months. Not only were they absent in mice that received Yamanaka factors for only one month, but also in mice analyzed halfway through the doses. This strongly hints that the treatment is not only pausing the aging process but actively winding back the aging clock. “In addition to tackling age-related diseases, this approach may provide the biomedical community with a new tool to restore tissue and organismal health by improving cell function and resilience in different disease situations, such as neurodegenerative diseases, ” notes professor Belmonte. “At the end of the day, we want to bring resilience and function back to older cells so that they are more resistant to stress, injury, and disease. This study shows that, at least in mice, there’s a path forward to achieving that .” The team now wants to look at the exact ways in which long-term treatment with Yamanaka factors alters certain genes and molecules. Credit: https://longevity.technology/news/can-cellular-rejuvenation-therapy-reverse-signs-of-aging-and-reset-cells/

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Cellular Rejuvenation Successfully Reverses Aging in Mice

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